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Dr. Bacanamwo’s laboratory is interested in understanding the role of chromatin remodeling and epigenetic mechanisms in gene expression regulation during the pathogenesis of cardiovascular diseases and the differentiation of vascular cells from stem cells. The long term objective is to develop epigenetic and other novel therapeutic and diagnostic strategies for cardiovascular diseases. We have established that vascular cell differentiation, vascular cell fate determination, and vascular function and lesion formation can be modulated by manipulation of the DNA methyltransferases, histone methyltransferases and demethylases, as well as histone acetyltransferases and deacetylases. Stem cells, various cellular and animal models of vascular diseases are being used along with pharmacological probes and genetic means of manipulating expression of the above epigenetics related genes. Patterns of epigenetic histone and DNA modification genomewide and at promoters and coding regions of specific genes are determined using state-of-the-art high throughput techniques such as ChIP-array, ChIP-Seq, bisulfite modification-Seq, and bisulfite modification-array. The epigenetic modification patterns are linked to gene expression profile changes during vascular cell differentiation from stem cells and during the pathogenesis of vascular diseases such as vascular remodeling, hypertension, obesity, etc… This simulation helps define the epigenetic mechanisms by which disease-promoting environmental conditions alter gene expression leading to the disease. The role of target genes altered epigenetically in the pathogenesis of cardiovascular diseases is further characterized using RNA interference (RNAi, mirRNA), forced gene expression, recombinant protein, and other pharmacological strategies along with routine molecular genetics and biochemistry techniques such as DNA arrays, quantitative real time PCR, various ELISA and Western blot techniques, chromatin immunoprecipitation assays, nuclear run-on, transient and stable transfections, promoter analysis.
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